Our goal is to evaluate the clinical activity of recombinant immunotoxins in patients. HA22 is licensed to MedImmune who is sponsoring trials in B cell malignancies. A multi center phase 1 trial of HA22 (CAT-8015, moxetumomab pasudotox) in drug resistant hairy cell leukemia is completed and is now being expanded at the MTD. There have been no dose limiting toxicities and over 50% of patients have achieved a complete remission. A multi center phase 1 trial of HA22 in refectory ALL has opened and 15 patients treated. Clinical activity with 4 complete remissions has been observed. This is a collaboration with Dr. Alan Wayne of the Pediatric Oncology Branch. Trials with LMB2 in CTL and ATL are ongoing. Dr. Hassan has treated 16 patients with mesothelioma with SS1P plus chemotherapy. An MTD has been established and at the MTD 6/9 patients have had PRs. We are now at the MTD and will treat 3more patients this dose level. Based on the high number of CRs at the MTD a randomized phase 2 trial is being planned. Another SS1P trial was just opened in which patients will receive pentostatin plus cyclophosphamide with SS1P to try and prevent neutralizing antibody formation allowing more doses to be given.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010020-16
Application #
8348946
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2011
Total Cost
$1,086,638
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Chandramohan, Vidyalakshmi; Pegram, Charles N; Piao, Hailan et al. (2017) Production and quality control assessment of a GLP-grade immunotoxin, D2C7-(scdsFv)-PE38KDEL, for a phase I/II clinical trial. Appl Microbiol Biotechnol 101:2747-2766
Hassan, Raffit; Alewine, Christine; Pastan, Ira (2016) New Life for Immunotoxin Cancer Therapy. Clin Cancer Res 22:1055-8
Bao, Xuhui; Pastan, Ira; Bigner, Darell D et al. (2016) EGFR/EGFRvIII-targeted immunotoxin therapy for the treatment of glioblastomas via convection-enhanced delivery. Receptors Clin Investig 3:
Hassan, Raffit; Thomas, Anish; Alewine, Christine et al. (2016) Mesothelin Immunotherapy for Cancer: Ready for Prime Time? J Clin Oncol 34:4171-4179
Pastan, Ira; Hassan, Raffit (2014) Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res 74:2907-12
Kelly, Ronan J; Sharon, Elad; Pastan, Ira et al. (2012) Mesothelin-targeted agents in clinical trials and in preclinical development. Mol Cancer Ther 11:517-25
Kreitman, Robert J; Tallman, Martin S; Robak, Tadeusz et al. (2012) Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol 30:1822-8
Mehta, Ankit I; Choi, Bryan D; Ajay, Divya et al. (2012) Convection enhanced delivery of macromolecules for brain tumors. Curr Drug Discov Technol 9:305-10
Sharon, Elad; Zhang, Jingli; Hollevoet, Kevin et al. (2012) Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary cancers. Clin Chem Lab Med 50:721-5
Mehta, Ankit I; Choi, Bryan D; Raghavan, Raghu et al. (2011) Imaging of convection enhanced delivery of toxins in humans. Toxins (Basel) 3:201-6

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